Gregory Lydall

Why medical students choose psychiatry - a 20 country cross-sectional survey

BackgroundRecruitment to psychiatry is insufficient to meet projected mental health service needs world-wide. We report on the career plans of final year medical students from 20 countries, investigating factors identified from the literature which influence psychiatric career choice.MethodsCross sectional electronic or paper survey. Subjects were final year medical students at 46 medical schools in participating countries. We assessed students’ career intentions, motivations, medical school teaching and exposure to psychiatry. We assessed students’ attitudes and personality factors. The main outcome measure was likelihood of specializing in psychiatry. Multilevel logistic regression was used to examine the joint effect of factors upon the main outcome.Results2198 of 9135 (24%) of students responded (range 4 to 91%) across the countries. Internationally 4.5% of students definitely considered psychiatry as a career (range 1 to 12%). 19% of students (range 0 to 33%) were “quite likely”, and 25% were “definitely not” considering psychiatry. Female gender, experience of mental/physical illness, media portrayal of doctors, and positive attitudes to psychiatry, but not personality factors, were associated with choosing psychiatry. Quality of psychiatric placement (correlation coefficient = 0.22, p < 0.001) and number of placements (correlation coefficient =0.21, p < 0.001) were associated with higher ATP scores. During medical school, experience of psychiatric enrichment activities (special studies modules and university psychiatry clubs), experience of acutely unwell patients and perceived clinical responsibility were all associated with choice of psychiatry.Multilevel logistic regression revealed six factors associated with students choosing psychiatry: importance of own vocation, odds ratio (OR) 3.01, 95% CI 1.61 to 5.91, p < 0.001); interest in psychiatry before medical school, OR 10.8 (5.38 to 21.8, p < 0.001); undertaking a psychiatry special study module, OR 1.45 (1.05 to 2.01, p = 0.03) or elective OR 4.28 (2.87- 6.38, p < 0.001); membership of a university psychiatry club, OR 3.25 (2.87 to 6.38, p < 0.001); and exposure to didactic teaching, OR 0.54 (0.40 to 0.72, p < 0.001).ConclusionsWe report factors relevant to medical student selection and psychiatry teaching which affect career choice. Addressing these factors may improve recruitment to psychiatry internationally.

Confirmation of prior evidence of genetic susceptibility to alcoholism in a genome-wide association study of comorbid alcoholism and bipolar disorder.

Objectives Alcoholism and affective disorders are both strongly comorbid and heritable. We have investigated the genetic comorbidity between bipolar affective disorder and alcoholism. Methods A genome-wide allelic association study of 506 patients from the University College London bipolar disorder case–control sample and 510 ancestrally matched supernormal controls. One hundred forty-three of the bipolar patients fulfilled the Research Diagnostic Criteria diagnosis of alcoholism. A total of 372 193 single nucleotide polymorphisms (SNPs) were genotyped. Genes previously shown to be associated with alcoholism and addiction phenotypes were then tested for association in the bipolar alcoholic sample using gene-wise permutation tests of all SNPs genotyped within a 50-kb region flanking each gene. Results Several central nervous system genes showed significant (P<0.05) gene-wise evidence of association with bipolar alcoholism. The genes implicated, which replicated genes previously shown to be associated with alcoholism were: cadherin 11, collagen type 11 &agr;2, neuromedin U receptor 2, exportin7, and semaphorin-associated protein 5A. The SNPs most strongly implicated in bipolar alcoholism, but, which did not meet conventional genome-wide significance criteria were the insulin-like growth factor-binding protein 7, carboxypeptidase O, cerebellin 2, and the cadherin 12 genes. Conclusion We have confirmed the role of some genes previously shown to be associated with alcoholism in the comorbid bipolar alcoholism subgroup. In this subgroup, bipolar disorder may lower the threshold for the phenotypic expression of these alcoholism susceptibility genes. We also show that some genes may independently increase susceptibility to affective disorder and alcoholism.

Support of association between BRD1 and both schizophrenia and bipolar affective disorder

A recent study published by our group implicated the bromodomain containing protein 1 (BRD1) gene located at chromosome 22q13.33 with schizophrenia (SZ) and bipolar affective disorder (BPD) susceptibility and provided evidence suggesting a possible role for BRD1 in neurodevelopment. The present study reports an association analysis of BRD1 and the neighboring gene ZBED4 using a Caucasian case–control sample from Denmark and England (UK/DK sample: 490 patients with BPD, 527 patients with SZ, and 601 control individuals), and genotypes obtained from a BPD genome wide association (GWA) study of an overlapping English sample comprising 506 patients with BPD and 510 control individuals (UCL sample). In the UK/DK sample we genotyped 11 SNPs in the BRD1 region, of which six showed association with SZ (minimal single marker P‐values of 0.0014), including two SNPs that previously showed association in a Scottish population [Severinsen et al. (2006); Mol Psychiatry 11(12): 1126–1138]. Haplotype analysis revealed specific risk as well as protective haplotypes with a minimal P‐value of 0.0027. None of the 11 SNPs showed association with BPD. However, analyzing seven BRD1 SNPs obtained from the BPD GWA study, positive associations with BPD was observed with all markers (minimal P‐value of 0.0014). The associations reported add further support for the implication of BRD1 with SZ and BPD susceptibility.

Genetic association study of GABRA2 single nucleotide polymorphisms and electroencephalography in alcohol dependence

The gamma aminobutyric acid (GABA) system has been implicated in the susceptibility to develop alcohol dependence and in determining electroencephalogram (EEG) beta activity. The role of the GABA receptor alpha-2 gene (GABRA2) in human alcohol dependence was determined in a genetic and electrophysiological study. The study population comprised 586 white UK individuals with alcohol dependence but a very low prevalence of co-morbid drug dependence, and 603 ancestrally matched healthy controls. Genotyping for seven GABRA2 single nucleotide polymorphisms (SNPs), identified from the literature as positively associated with alcohol dependence, was performed with success rates of 90% or greater. EEGs were available in 32 selected patients who had been abstinent from alcohol for a minimum of 24 months and in 138 ancestrally matched healthy controls. None of the SNPs showed allelic or haplotypic association with alcohol dependence. All markers were in Hardy Weinberg equilibrium (HWE) in the controls. HWE for marker rs279841 in the alcohol dependent sample was p=0.0199 and combined p=0.0166. Linkage disequilibrium patterns appear to be very similar to that observed in the HapMap CEU data. A significantly higher prevalence of excess EEG fast activity was found in the patients (31 vs. 14%, p=0.018). A significant relationship was found between the presence of excess EEG fast activity and GABRA2 SNPs rs548583, rs279871 and rs279841. This allelic association study provides no evidence for an association between GABRA2 polymorphisms and alcohol dependence. However, a significant relationship was identified between GABRA2 and excess EEG fast activity. This dissociation of effect may reflect the fact that the EEG is a more direct marker of phenotypic GABRA2 expression than the more heterogeneous alcohol dependence phenotype.

What attracts medical students towards psychiatry? A review of factors before and during medical school

Abstract Potential psychiatrists decide on their careers before, during or after medical school. This article summarises the literature focusing on the first two groups. Pre-medical school factors associated with choosing psychiatry include gender, academic aptitude, ethnicity and migration, exposure to mental illness, economic considerations and medical school route and selection. Factors involved in influencing career choice at medical school level include attitudes towards psychiatry, teaching methods, quality and length of clinical exposure, electives and enrichment activities, and personality factors. Considering these factors may improve recruitment to psychiatry and address shortages in the speciality.

Genetic variants in or near ADH1B and ADH1C affect susceptibility to alcohol dependence in a British and Irish population.

Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol dehydrogenase (ADH) enzymes confer a significant protective effect against alcohol dependence syndrome (ADS) in East Asian populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in European populations. To further elucidate these associations, SNPs of interest in ADH1B, ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish population (ADS cases n = 1076: controls n = 1027) to assess their relative contribution to ADS risk. A highly significant, protective association was observed between the minor allele of rs1229984 in ADH1B and ADS risk [allelic P = 8.4 × 10−6, odds ratio (OR) = 0.26, 95 percent confidence interval, 0.14, 0.49]. Significant associations were also observed between ADS risk and the ADH1B/1C intergenic variant, rs1789891 [allelic P = 7.2 × 10−5, OR = 1.4 (1.2, 1.6)] and three non‐synonymous SNPs rs698, rs1693482 and rs283413 in ADH1C. However, these associations were not completely independent; thus, while the ADH1B rs1229984 minor allele association was independent of those of the intergenic variant rs1789891 and the three ADH1C variants, the three ADH1C variants were not individually independent. In conclusion, the rare ADH1B rs1229984 mutation provides significant protection against ADS in this British and Irish population; other variants in the ADH gene cluster also alter ADS risk, although the strong linkage disequilibrium between SNPs at this location precluded clear identification of the variant(s) driving the associations.

Encouraging French medical students to choose a career in psychiatry: How and why?

Abstract There is an increasing demand for psychiatrists in France. This paper reviews the reasons for French medical students choosing psychiatry and the rationale and mechanisms for encouraging them towards this medical speciality. The main factors associated with choosing psychiatry as a career are the quantity and quality of undergraduate training and placements in psychiatry, better attitudes towards psychiatry and more emphasis on a positive life/work balance. The quality of postgraduate training can also influence students’ decisions. Medical students should be encouraged to choose psychiatry first to counterbalance the existing stigma towards mental illness within the society, but also towards psychiatry within the medical profession, and second because of the current decline in French medical demography. Ways to improve recruitment are a selection process that favours a large number of psychiatric trainees, and an increase in the quality and quantity of training. Providing medical students with relevant information about training in psychiatry, notably through a national trainees’ association, will not only improve the quality of care by increasing recruitment in psychiatry, but also ensure that all future doctors are familiar with and develop positive attitudes towards mental health issues.

Research into recruitment: Critical gaps in the literature

Abstract The aim of this paper is to systematically review the literature available internationally on recruitment into psychiatry. A 5-stage search strategy was followed to identify all relevant studies published between 1999–2012. These were then critically appraised using a standardized tool, and the results summarized. A total of 128 studies were identified. Surveys were the most common design (40%), and 76% of studies used medical students as subjects; 36% of the studies were from the USA, followed by 25% from the UK. There were no studies found from South America. There is a need for more research into other potential applicant groups before medical school, and for research carried out in Africa, Asia and South America.

Lack of allelic association between markers at the DRD2 and ANKK1 gene loci with the alcohol-dependence syndrome and criminal activity

and ANKK1 gene loci with the alcohol-dependence syndrome and criminal activity Katherine Kasiakogia-Worlley, Andrew McQuillin, Gregory John Lydall, Shamir Patel, Girija Kottalgi, Priyanthi Gunwardena, Raquin Cherian, Harsih Rao, Audrey Hillman, Nallananathan Gobikrishnan, Ewen Douglas, Sherhzad Yameen Qureshi, Sameer Jauhar, David Ball, Aideen O’Kane, Lynne Owens, Alex Dedman, Sally Isobel Sharp, Radhika Kandaswamy, Irene Guerrini, Allan D. Thomson, Iain Smith, Karim Dar, Marsha Yvonne Morgan and Hugh Malcolm Douglas Gurling

Evidence for genetic susceptibility to the alcohol dependence syndrome from the thiamine transporter 2 gene solute carrier SLC19A3.

The risk for developing the alcohol dependence syndrome (ADS) has a substantial genetic component. The human thiamine transporter protein 2 (hTHTR2) is encoded by the SLC19A3 gene, which is on chromosome 2q37. hTHTR2 is responsible for the cellular uptake of thiamine (B1), a water-soluble essential vitamin that plays a fundamental and ubiquitous role in carbohydrate metabolism. This gene was also found to be associated with biotin-responsive basal ganglia disease, an autosomal recessive metabolic disorder characterized by encephalopathy and ophthalmoplegia (Ozand et al., 1998; Zeng et al., 2005). Homozygous or compound heterozygous mutations in SLC19A3 cause two distinct clinical phenotypes: biotin-responsive basal ganglia disease and Wernicke’s-like encephalopathy. Biotin and/or thiamine are effective therapies for both diseases (Yamada et al., 2010). A missense mutation in exon 5 of the SLC19A3 was found in 18 cases of biotin/thiamine-responsive basal ganglion disease presenting with subacute encephalopathy and extrapyramidal signs (Alfadhel et al., 2013). Kono et al. (2009) described two Japanese brothers, who were both compound heterozygotes for the K44E and E320Q mutations in SLC19A3, who developed a syndrome of thiamine-responsive diplopia, ophthalmoplegia and ataxia, similar to Wernicke’s encephalopathy, despite normal serum thiamine levels (Kono et al., 2009). Yamada et al. (2010) reported a pathogenic homozygous mutation (c.958G>C, [p.E320Q]) in SLC19A3 in four patients from a single family. They report a wide variety of neurological signs in SLC19A3 mutation carriers. Our previous unpublished research found that four markers in the SLC19A3 gene showed significant allelic association with Wernicke–Korsakoff syndrome (WKS) in a sample of 120 cases when compared with normal controls. In the present study, the entire SLC19A3 gene was screened for DNA variation in a WKS subset (n=120) of a UK ADS case–control sample comprised of 1032 alcohol-dependent cases and 1022 controls. High resolution melting curve analysis, which is based on the melting characteristic of double-stranded DNA, was carried out using a LightCycler 480 Real-Time PCR System (Roche, Burgess Hill, UK). Genetic variation was validated with Sanger DNA sequencing. Thirteen single nucleotide variants were identified through high resolution melting analysis. Two exon 3 variants that were predicted to cause amino acid substitutions, 2:228563818T/C and rs148144444, were selected for genotyping in the entire ADS case–control sample using an allele-specific fluorescent PCR method (KasPar; LGC Genomics, Hoddesdon, UK). Statistical analysis was carried out on the previously unreported 2:228563818T/C change of a T to C substitution at position 228 563 818 on chromosome 2. This variant causes an R250G amino acid substitution in the largest cytoplasmic domain of the protein and it is, therefore, likely to affect post-translational function. rs148144444 causes the amino acid change G141S which is likely to exert an effect on protein phosphorylation and conformation because of the introduction of the aliphatic chain of serine. Neither the cases nor the controls in the present study had the SLC19A3 disease susceptibility variants that have been reported previously (Zeng et al., 2005; Kono et al., 2009). The minor allele of 2:228563818T/C was detected in five ADS cases, but was absent in the control samples (P=0.033). The minor allele of rs148144444 was detected in five ADS cases and in four controls and was not associated with ADS. Neither of these variants was present in the 120 WKS cases in our ADS sample. Our data suggest that genetic variation in the SLC19A3 thiamine transporter at 2:228563818T/C may make a modest contribution towards the genetic susceptibility to ADS.